breast cancer MedDRA version: 20.0 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10061020 Term: Breast cancer male System Organ Class: 10029104 - Neoplasms benign, mal
Conditions
Interventions
Product Name: tesetaxel
Product Code: DJ-927
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Tesetaxel
CAS Number: 333754-36-2
Sponsors
Odonate Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All of the following criteria must be met: 1. Female or male patients at least 18 years of age 2. Histologically or cytologically confirmed breast cancer 3. HER2 negative disease based on local testing: American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines should be utilized for assessing HER2 status 4. HR (estrogen receptor [ER] and/or progesterone receptor [PgR]) positive disease based on local testing: ASCO/CAP guidelines should be utilized for assessing HR status 5. Measurable disease per RECIST 1.1, including bone-only disease with measurable lytic component - Patients with bone-only metastatic cancer must have a measurable lytic or mixed lytic-blastic lesion that can be accurately assessed by computerized tomography (CT) or magnetic resonance imaging (MRI). Patients with bone-only disease without a measurable lytic component (ie, blastic-only metastasis) are not eligible. - Known metastases to the CNS are permitted but not required. The following criteria apply: - Patients must be neurologically stable and either off corticosteroids or currently treated with a maximum daily dose of 4 mg of dexamethasone (or equivalent), with no increase in corticosteroid dose within 7 days prior to Enrollment (defined as the time of Sponsor approval of treatment dose) - Patients with a history of CNS metastases but with no current evidence of CNS lesions following local therapy are eligible - Patients may have CNS metastases that are stable or progressing radiologically - Patients with current evidence of leptomeningeal disease are not eligible - Patients may have untreated brain metastases or previously treated brain metastases, as long as no immediate local CNS-directed therapy is indicated - Any prior whole brain radiation therapy must have been completed > 14 days prior to the date of Enrollment - Prior stereotactic brain radiosurgery is permitted - CNS surgical resection must have been completed > 28 days prior to the date of Enrollment; patient must have complete recovery from surgery 6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 7. Prior endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor unless endocrine therapy is not indicated (ie, short relapse-free interval while on adjuvant endocrine therapy [endocrine resistance]; rapidly progressing disease/visceral crisis; or endocrine intolerance). Any targeted therapies approved for HER2 negative, HR positive LA/MBC, including everolimus, are permitted as prior therapy. There is no limit to the number of prior endocrine therapies. 8. Documented (including de novo): (a) locally advanced breast cancer that is not considered curable by surgery and/or radiation; or (b) metastatic breast cancer 9. Adequate hematologic, hepatic, and renal function, as evidenced by: - Absolute neutrophil count (ANC) = 1,500/µL without colony-stimulating factor support - Platelet count = 100,000/µL - Hemoglobin = 10 g/dL without need for hematopoietic growth factor or transfusion support - Total bilirubin < 1.5 × upper limit of normal (ULN); does n
Exclusion criteria
Exclusion criteria: 1. Two or more prior chemotherapy regimens for advanced disease 2. Prior treatment with a taxane at any dose 3. Prior treatment with capecitabine at any dose 4. Current evidence of leptomeningeal disease 5. Other cancer that required therapy within the preceding 5 years other than adequately treated: (a) non melanoma skin cancer or in situ cancer; or (b) following approval by the Medical Monitor, other cancer that has a very low risk of interfering with the safety or efficacy endpoints of the Study 6. Known human immunodeficiency virus infection, unless well controlled. Patients who are on an adequate antiviral regimen with no evidence of active infection are considered well controlled. 7. Active hepatitis B or active hepatitis C infection 8. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with Study participation or investigational product administration or may interfere with the interpretation of Study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this Study 9. Presence of neuropathy > Grade 1 per NCI CTCAE version 5.0 10. Anticancer treatment, including endocrine therapy, radiotherapy (except stereotactic brain radiosurgery), chemotherapy, biologic therapy, or therapy in an investigational clinical study, = 14 days prior to the date of Enrollment 11. Major surgery = 28 days prior to the date of Enrollment; patient must have complete recovery from surgery 12. Less than 2 weeks or 5 plasma half-lives (whichever is greater) since last use of a medication or ingestion of an agent, beverage, or food that is a known clinically relevant strong inhibitor or known clinically relevant inducer of the cytochrome P450 (CYP)3A pathway (patients should discontinue taking any regularly-taken medication that is a strong inhibitor or inducer of the CYP3A pathway) 13. History of hypersensitivity or unexpected reactions to capecitabine, fluoropyrimidine agents or any of their ingredients 14. Known dihydropyrimidine dehydrogenase (DPD) deficiency. Testing for DPD deficiency must be performed where required by local regulations, using a validated method that is approved by local health authorities. 15. Pregnant or breastfeeding 16. If, in the opinion of the Investigator, the patient is deemed unwilling or unable to comply with the requirements of the Study 17. Treatment with brivudine, sorivudine, or its chemically-related analogs = 28 days prior to the date of Enrollment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: No interim analyses for purposes of early stoppage of the Study are planned. The projected timing for evaluation of the primary endpoint is approximately 2 - 2.5 years following Study initiation. ;Main Objective: To establish the efficacy of tesetaxel plus a reduced dose of capecitabine in patients with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive, locally advanced or metastatic breast cancer (LA/MBC) not previously treated with a taxane in the neoadjuvant, adjuvant, or metastatic setting; Secondary Objective: SECONDARY OBJECTIVE - To assess the safety and tolerability of tesetaxel plus a reduced dose of capecitabine in patients with HER2 negative, HR positive LA/MBC not previously treated with a taxane in the neoadjuvant, adjuvant, or metastatic setting PHARMACOKINETIC OBJECTIVES - To investigate the relationship between the pharmacokinetics (PK) of tesetaxel and efficacy and safety endpoints in patients with HER2 negative, HR positive LA/MBC not previously treated with a taxane in the neoadjuvant, adjuvant, or metastatic setting - To investigate the potential for a PK drug-drug interaction of tesetaxel on capecitabine and its active metabolite, fluorouracil (5-FU) ; Primary end point(s): The primary endpoint is objective response rate (ORR) as assessed by an Independent Radiologic Review Committee (IRC). The ORR is defined as the proportion of patients who achieve a best overall response of complete response (CR) or partial response (PR) per RECIST 1.1. The ORR with the exact binomial 95% confidence interval (CI) will be reported. The primary efficacy analysis will require confirmation of response on subsequent assessment at least 4 weeks after the initial assessment and will be based on tumor assessments by the IRC. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: No interim analyses for purposes of early stoppage of the Study are planned. The projected timing for evaluation of secondary endpoints (relative to Study initiation) is summarized here: SECONDARY EFFICACY ENDPOINTS: - DoR: approx. 2-2.5 years - PFS: approx. 2-2.5 years - DCR: approx. 2-2.5 years - OS: approx. 3-3.5 years CNS METASTASES EFFICACY ENDPOINTS: - CNS ORR: approx. 2-2.5 years - CNS DoR: approx. 2-2.5 years - CNS PFS: approx. 2-2.5 years - CNS OS: approx. 3-3.5 years SAFETY ENDPOINTS: - Incidence of TEAEs: approx. 3-3.5 years - Incidence of clinical laboratory abnormalities: approx. 3-3.5 years PHARMACOKINETIC ENDPOINTS: - Cmax and AUC of tesetaxel: approx. 2-2.5 years - Cmax and AUC of capecitabine and 5-FU: approx. 2-2.5 years ; Secondary end point(s): SECONDARY EFFICACY ENDPOINTS (in order of importance): ? Duration of response (DoR) as assessed by the IRC - DoR = time from date of first tumor assessment with documented response (CR or PR) according to RECIST 1.1 to date of disease progression or death using the same rules and censuring rules applied to PFS - Kaplan-Meier statistics will follow those presented for PFS ? Progression-free survival (PFS) as assessed by the IRC - PFS = time from Treatment Initiation to first observed PD or death by any cause - PFS of patients with death or PD after two or more missed radiologic disease assessment visits will be censored at the last evaluable PFS assessment by the IRC - Distributions of PFS times will be estimated using the Kaplan Meier product-limit | — |
Countries
Australia, Canada, Korea, Republic of, Spain, Taiwan, Ukraine, United States
Contacts
Public ContactChief Development Officer
Odonate Therapeutics, Inc.
Outcome results
None listed